Synergistic effect of glucocorticoids on the stimulation of progesterone production by follicle-stimulating hormone in cultured rat granulosa cells.
The direct effects of adrenocortical steroids on basal and FSH-stimulated production of progesterone by ovarian granulosa cells were investigated in vitro. Granulosa cells from immature, hypophysectomized, estrogen-treated rats were cultured for 2 days in the presence or absence of FSH and/or corticoids. Treatment with FSH resulted in substantial increases in the accumulation of progesterone, whereas dexamethasone by itself was only minimally effective. However, concomitant treatment with increasing concentrations of various native and synthetic corticoids led to dose-dependent increases (200-500%) in the FSH-stimulated accumulation of progesterone. The stimulatory potencies of the corticoids tested correlated with their glucocorticoid rather than their mineralocorticoid potencies (dexamethasone greater than cortisol much greater than aldosterone). Treatment with dexamethasone also led to significant increases in the accumulation of progesterone stimulated by prostaglandin E2, cholera toxin, or dibutyryl cAMP. In the presence or absence of FSH, treatment with dexamethasone, cortisol, or corticosterone led to significant decreases in the activity of 20 alpha-hydroxysteroid dehydrogenase. In addition, treatment with dexamethasone led to significant increases in basal and FSH-stimulated activities of 3 beta-hydroxysteroid dehydrogenase. Our findings indicate that glucocorticoids synergize with FSH and other trophic agents in the accumulation of progesterone in accordance with their glucocorticoid rather than mineralocorticoid potencies and that this direct effect may be accounted for, at least in part, by the stimulation of 3 beta-hydroxysteroid dehydrogenase and the inhibition of 20 alpha-hydroxysteroid dehydrogenase.
D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004054:Diethylstilbestrol / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006854:Hydrocortisone / Q000494:pharmacology; D007016:Hypophysectomy; D007700:Kinetics; D011374:Progesterone / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D005938:Glucocorticoids; D000450:Aldosterone; D011374:Progesterone; D004054:Diethylstilbestrol; D003907:Dexamethasone; D005640:Follicle Stimulating Hormone; D006854:Hydrocortisone